Day 10 rat embryos were cultured in rat serum in the presence of 20-80 mug Ni as nickel chloride (NiCl(2))/ml of culture medium, or in serum taken from rats, on day 10 of pregnancy, 1 hr after ip injection of 4 mg Ni/kg body weight (as NiCl(2)). Embryos were exposed to these mediums either for 26 or for 4 hr, and were then transferred to fresh serum for the remainder of the 26-hr culture period. Normal development was observed in embryos cultured in serum from treated females (which was found to contain about 17 mug Ni and 3.4 mg glucose/ml) or in 20 mug Ni/ml (as NiCl(2)) added directly to the culture medium. Some embryos were killed by exposure to 80 or 40 (or more) mug Ni/ml for 4 or 26 hr, respectively. Regardless of the duration of exposure, malformations appeared at 30 mug Ni/ml primarily in the cephalic region. Reduced caudal neural tube and branchial arches, and dilated optic vesicles were observed in embryos exposed to 40 mug Ni/ml for 26 hr. High incidences of poor yolk-sac circulation and incomplete turning, and significant decreases in yolk-sac diameter and number of somite pairs were observed in embryos exposed to 60 or 70 mug Ni/ml for 4 hr, or to 30 to 40 mug Ni/ml for 26 hr. Our results indicate that the early maternal blood consequences of a single ip injection of NiCl(2) in mid-gestation are harmless to the development of day 10 cultured embryos and that nickel is embryotoxic in vitro at concentrations that are probably not reached in vivo under these maternal treatment conditions.