A subchronic toxicity study of calcium lactate was carried out in male and female F344 rats to estimate the maximum tolerated dose for a subsequent long-term toxicity/carcinogenicity study. Experiment I: Rats were divided into 6 groups, each consisting of 5 males and 5 females. Calcium lactate was dissolved in water at concentrations of 5, 2.5, 1.25, 0.6, 0.3 and 0%, each animal group was given one of these solutions as the drinking water for 13 wk. In all groups, basic diet (CRF-1) was given ad libitum. No fatalities occurred. In all treated groups, including the 5% group, a less than 10% depression of body-weight gain as compared with the control group was observed. Some parameters in the hematological and biochemical data demonstrated change in the treated groups. On histological examination, however, no severe toxicological findings were found in any of the treated groups. Experiment II: Rats were fed synthetic diet B, containing 30, 20, 10, 5 or 0% calcium lactate. In the highest dose group, body weight-gain was strongly reduced as compared with the control group. Histological examination revealed nephrocalcinosis in all groups, including the control group, and adverse dose-effect relation was observed with regard to degree of its development. Females exhibited this lesion to a greater extent than males. Experiment III: Rats were given CRF-1 or synthetic diet B for 8 wk. Nephrocalcinosis was found only in the group given synthetic diet. It was ascertained that the nephrocalcinosis observed in Exp. II and III was dependent on the low Ca/P ratio (Ca/P: less than 1) of the synthetic diet B.(ABSTRACT TRUNCATED AT 250 WORDS)