Prostaglandin (PG) E and F output was studied in collagenase-dispersed amnion cells to determine the effect of extracellular Ca2+ upon PG synthesis. In the presence of 2.5 mM CaCl2, PGE and PGF output (picograms per 105 cells per 3 h) by cells obtained at term prior to labour following elective cesarean section (CS) was 183 ± 39 and 127 ± 23, respectively. This increased to 435 ± 111 (p < 0.025) and 241 ± 49 (p = 0.056) from cells obtained after spontaneous labour and delivery at term (SL). Exclusion of CaCl2 from the medium (plus 0.1 mM EGTA) significantly reduced (p < 0.025) PGE output in CS and SL cells (83 ± 22 and 183 ± 47, respectively) and PGF output in CS cells (70 ± 17). PGE output in both CS and SL cells was unchanged when CaCl2 concentrations in the medium were decreased from 2.5 to 0.25 mM, but significantly attenuated (p < 0.01) when extracellular CaCl2 was decreased from 0.25 to 0 mM. The voltage-sensitive Ca2+ channel blocker, D-600, decreased PGE output in the presence of (2.5 mM) CaCl2 to levels observed in the absence of CaCl2. Ionophore A23187 restored PGE output in the presence of D-600 and Ca2+. PGF output from CS amnion cells was stimulated by A23187 and elevated extracellular K+ (40 mM). In each case, exclusion of CaCl2 from the medium eliminated the response. These, results suggest that PG output by human amnion is dependent, in part, upon the presence of extracellular Ca2+ and that Ca2+ may enter the cell via a potential-sensitive mechanism.