This study was designed to examine the characteristics of cadmium bioaccumulation by human trophoblast cells in culture and the subsequent effect of cadmium exposure on progesterone production and syncytial formation. The accumulation of cadmium suggested a time- and dose-dependent relationship, although it was not significant. The rate of metal accumulation was similar in all cadmium-treated groups. After 72 h of continuous exposure to cadmium concentrations of 5, 10, and 20 microM, progesterone release was diminished to 69, 51, and 38% of control values (P < 0.05), respectively. When cells were exposed to cadmium from 72 to 96 h (after syncytial development), progesterone release exhibited the same pattern of decline in response to increasing cadmium concentrations. Histologic evaluation of whole mounts of trophoblast cells exposed to 20 microM CdCl2 for 96 h revealed that syncytial formation seemed to be uninhibited. The pattern of cadmium-accumulation by normal cultured human trophoblast cells suggests a time- and dose-relationship with a concomitant decrease in progesterone release that occurs without apparent inhibition of syncytial development.