The effects of some aromatic hydrocarbons, aliphatic chlorinated hydrocarbons, and alcohols on adenosine triphosphatase (ATPase) activity in human erythrocyte ghost membrane were studied in vitro. Both aromatic and chlorinated aliphatic hydrocarbons inhibited this activity dose-dependently, the inhibition of total ATPase activity being clearer than that of magnesium-activated ATPase. Of the alcohols studied, methanol had no effect on the ATPase activity, but ethanol, propranolol, and butanol were slightly enzyme-activating at high concentrations. The enzyme-inhibiting potency of organic solvents was generally related to their lipid solubilities, but 1,1,2,2-tetrachloroethane was a potent enzyme inhibitor despite its low lipid solubility. This findings indicates that, eg, the molecular structure of solvents may modulate their enzyme inhibition. In the presence of Triton-X-100, toluene did not cause any changes in the activity of total ATPase, and the combined effect of the two compounds was slight. Triton-X-100 also caused a significant solubilization of membrane proteins although even the highest toluene concentrations did not. These results show that organic solvents may cause their membrane effects by acting directly on membrane-bound integral proteins such as ATPase. This action is not only dependent on the lipid solubility of the compounds, but also on their molecular structure.