The alpha-helical coiled-coil tropomyosin homodimer; alpha alpha Tm, unfolds cooperatively with T-1/2 = 47 degrees C, at neutral pH, 0.5 M NaCl. At pH 2, where each chain contains 55 positive charges, no cooperative unfolding occurs to at least 80 degrees C. The NaCl and K2SO4 dependence of thermal unfolding of alpha alpha Tm and a less stable protein, beta beta Tm, were studied with circular dichroism. For alpha alpha Tm, 10 mM NaCl, or 0.5 mM K2SO4, was sufficient to increase the unfolding temperature by 80 degrees C. For beta beta Tm, similar concentrations of NaCl and K2SO4 as for alpha alpha Tm increased the unfolding temperature of the most stable domain, Titrations indicated that two to three anions bind preferentially to the beta beta Tm intermediate. Thus anions bind to Tm at acid pH values to greatly stabilize the helix. But even in the absence of added salt, Tm is more stable at pH 2 than pH 7, suggesting destabilization by negatively charged amino acids.