The present investigation was designed to study the possible role of intrasperm Ca(2+) in spermicidal action of H(2)-receptor antagonists. Influence of commonly used H(2)-receptor antagonists cimetidine, ranitidine and famotidine on sperm viability and intrasperm Ca(2+) was evaluated in ejaculated human semen samples. All these drugs were found to reduce sperm viability in a dose- and time-dependent manner. This action was accompanied with elevation of intrasperm Ca(2+). 2', 4'-dichlorobenzamil hydrochloride (DBZ), a Na(+)-Ca(2+) exchange inhibitor, that is known to elevate intrasperm Ca(2+), potentiated the spermicidal action of H(2)-receptor antagonists. Intrasperm Ca(2+) was found to rise at much faster rate when DBZ was combined with any of the three H(2)-receptor antagonists. Due to this, the maximum Ca(2+) level required to produce death of sperm cells was attained much earlier as compared to the per se effect of any one of these drugs. These results suggest that elevation of intrasperm Ca(2+) by H(2)-receptor antagonists plays a key role in influencing sperm viability.