Maternal and fetal 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and osteocalcin were measured in guinea pigs, to examine their potential use as animal models for fetal bone development and calcium homeostasis. Measurements were performed on days 42, 57 and 63 of gestation. Maternal serum total 1,25(OH)2D3 concentrations were increased only at the end of gestation (day 63). However, because the vitamin D binding protein (DBP) and albumin levels were decreased by 35-50% from day 42 onwards, the unbound 1,25(OH)2D3, calculated as the 1,25(OH)2D3/DBP molar ratio, was increased before day 63. Osteocalcin concentrations during gestation were 50-54% of levels found in nongravid animals. Fetal serum total 1,25(OH)2D3 concentrations were 20% of those in maternal guinea pigs. Since DBP levels were only 9-15% of maternal levels, the unbound 1,25(OH)2D3 was consistently higher in fetuses, from day 42 onwards. There was a rise in total and unbound 1,25(OH)2D3 between days 57 and 63 of fetal life. Osteocalcin concentrations were higher in fetal than in adult guinea pigs, and reached peak values on day 57 (1023 micrograms/l, i.e. 4.2 times higher than in adult female guinea pigs). Fetuses of guinea pigs that had received a restricted food supply for 14 days (days 49-63) had normal 1,25(OH)2D3 concentrations, but decreased osteocalcin concentrations compared with normal fetuses. The data obtained in fetal guinea pigs are comparable with those found in human fetuses, and suggest that the guinea pig may be a suitable model for studies on fetal bone and mineral development.