Previous experiments have shown that long-term cyclosporine treatment in rats causes decreased systolic pressure development at any given preload of the left ventricle. The current experiments were designed to investigate the force-length and force-calcium relationship of papillary muscles from the right ventricles of rats that had received 15 mg/kg/day of cyclosporine subcutaneously for 3 weeks. Cyclosporine caused an increase of passive force at all muscle lengths, independent of the calcium concentration [Ca2+]o. Furthermore, cyclosporine enhanced twitch force at all muscle lengths at low [Ca2+]o relationship showed a decrease in the [Ca2+]o at which 50% of maximal force was generated in cyclosporine-treated muscle preparations compared with controls; at [Ca2+]o above 2.4 mmol/L, active force decreased by approximately 20% in muscles from cyclosporine-treated animals. The maximal force developed by papillary muscles from cyclosporine-treated animals was not different from that of control muscles: 45 mN/mm2 cross-sectional area, compared with 53 mN/mm2 respectively. We conclude that cyclosporine treatment causes increase in sensitivity for extracellular calcium, very likely reflecting an increased intracellular calcium concentration which, in the rat, may lead to calcium overload and decreased force development.