The electron/hole conduction of disordered bulk double-stranded (ds) calf thymus DNA and of one-dimensionally aligned 12-base pair single- and double-stranded oligonucleotide monolayers on gold was probed by testing for the occurrence of Faradaic processes. The disordered ds-DNA film was probed by doping it with soybean peroxidase, an easy to "wire" thermostable polycationic enzyme and measuring the current density of electroreduction of H2O2 to water at SCE potential. Although the current density in films with hydrophilic electron-conducting polymeric "wires" is similar to 0.5 mAcm(-2), when ds-DNA was used to "wire" soybean peroxidase, the current density was only 0.1 mu A cm(-2), similar to that in the absence of an electron-conducting enzyme-"wiring" polymer. We conclude that the diffusivity of electrons in unaligned and unstretched calf thymus DNA is less than 10(-11) cm(2) s(-1). Nevertheless, the occurrence of a Faradaic reaction was observed in the Au-S-(CH2)(2)-ds-oligo-NH-PQQ/Au-S-CH2-CH2-OH monolayer on gold, in which the helices were one-dimensionally aligned and comprised a >30 Angstrom ds-oligonucleotide segment. In these the rate constant for PQQ electrooxidation-electroreduction was 1.5 +/- 0.2 s(-1), only about 4-fold less than the 5 +/- 1 s(-1) constant for the reference Au--S--(CH2)(2)--NH--PQQ monolayer. When two mismatches were introduced in the 12 base-pair ds-oligonucleotide (by C --> A and C --> T substitutions) the constant decreased to 0.6 +/-0.2 s(-1). In contrast, the rate for the Au-S-(CH2)(2)-ss-oligo-NH-PQQ/Au-S-CH2-CH2-OH monolayer was too small to be measured; no voltammetric waves were detected at a scan rate of 10 mV s(-1). The anisotropic conduction in the one-dimensionally ordered solid ds-DNA films is attributed to the concerted movement of cations in the direction of the main axes of the ds-helices when an electric field is applied. Such movement causes the high-frequency longitudinal (not the high-frequency transverse optical) polarizability to be high and thereby makes the resolved component of the high-frequency dielectric constant high. The solid ds-DNA films also contain less water than their solutions, which reduces the static dielectric constant relative to that of water. As shown by Mott and Gurney, reduction of the difference between the static dielectric constant and the high-frequency longitudinal dielectric constant increases the mean free path and the mobility of electrons in an ionic solid and makes ds-DNA a one-dimensional semiconductor. The high frequency dielectric constant, as described in textbooks on solid-state physics, also decreases the ionization energies of donors and greatly extends their Bohr-radii, which are sausage-shaped in ds-DNA. A likely n-type dopant is the G-base in the GC base pair, a dopant ionized ("oxidized") in the high-frequency dielectric constant medium. The proposed biological function of the insulator-to-semiconductor transition upon parallel alignment of the ds-DNA is protection against irreversible chemical change by oxidation or reduction. Removing or adding of an electron produces in an insulator a localized reactive radical. Adding a hole or an electron to a band of a semiconductor, which extends Over a large number of atoms, does not make any atom in the ensemble uniquely reactive.