The in vitro effects of the insecticide lindane have been investigated in rat testis peritubular myoid cells (PMCs). Upon PMC exposure to lindane, polarity increase and decrease of dipole dynamics were seen at the membrane level (EC50 20 microM), leading to a partial dissipation of the membrane intrinsic dipole potential. The initial membrane depolarization was increased by Cl- efflux and limited by Ca(2+)-activated repolarizing currents. Concomitantly, lindane produced an increase in [Ca2+]i (EC50 125 microM) resulting from both Ca2+ release from an inositol 1,4,5-trisphosphate-sensitive intracellular store and a voltage-dependent Ca2+ influx from the extracellular medium. Of particular interest from a toxicologic point of view, insecticide concentrations well below those effective in altering ion homeostasis potently inhibited both [Ca2+]i increase and contraction induced by the natural agonists vasopressin and endothelin-1 (IC50s < 10 microM). These data demonstrate that PMCs are highly susceptible to lindane and suggest that the insecticide may exert testicular toxicity by interfering with hormone-regulated PMC function.