The helix-coil transition of poly[d(I-C)] and poly[d(A-T)] was studied as a function of hydrostatic pressure, temperature, and sodium ion concentration. These studies were undertaken in light of a recently published phase diagram for double stranded nucleic acids [Dubins et al. J. Am. Chem. Soc. 2001, 123, 9254-9259]. The sign and magnitude of the volume change for the heat-induced helix-coil transition, Delta V-T, of poly[d(I-C)] and poly[d(A-T)] were dependent on the helix-coil transition temperature, T-M, at atmospheric pressure. The sign of Delta V-T changed from negative to positive as T-M was increased by increasing the sodium ion concentration. For poly[d(I-C)], Delta V-T = 0 cm(3) mol(-1), when the sodium ion concentration is such that the spectroscopically monitored T-M = 55 degrees C at atmospheric pressure. For poly[d(A-T)], the value of Delta V-T = 0 under conditions such that T-M = 47 degrees C at atmospheric pressure. Negative values of Delta V-T imply that the helical form is destabilized at high pressure. Under experimental conditions where the Delta V-T for the transition is negative, the transition could be caused by increasing the pressure under isothermal conditions. At temperatures below T-M measured at atmospheric pressure the midpoint of the pressure-induced helix-coil transition, P-M, decreases with increasing temperature. The volume change of the pressure-induced transitions helix-coil transition, Delta V-P, was calculated assuming a two-state model. The magnitude of Delta V-P (per cooperative length) was much larger than the volume change (per base pair) measured for the heat-induced transition, Delta V-T, calculated using the Clapeyron equation. The ratio of these two volume changes was used to calculate the cooperative length for the pressure-induced transition. This parameter depends strongly on temperature, becoming greater closer to T-M measured at atmospheric pressure. At temperatures approaching T-M the magnitude of the cooperative length of the pressure-induced transition is approximately twice that observed for the heat-induced transition (N-T). On the basis of the temperature dependence of the Delta V-T for the two polymers the coefficient of thermal expansion of the two polymers was found to be 0.17 and 0.16 cm(3) K-1 mol(-1) for poly[d(I-C)] and poly[d(A-T)], respectively.