Erythrocyte (RBC) galactokinase (GALK) and galactose-1-phosphate uridylyl-transferase (GALT) activities were measured in a random sample of 1,700 (1.082 black and 618 white) pregnant women from the Philadelphia area to estimate the frequency of the genes GALKG and GALTG responsible for the two biochemically distinct forms of galactosemia. Blacks have significantly lower mean RBC GALK activities than whites (P less than .0005). The distribution of individual GALK activities for blacks differs from a normal distribution (X227=43.0, P less than .03) whereas that for whites does not (X224=25.5, P approximately equal to .30). These results are consistent with the thesis that reduced RBC GALK activity in blacks is due to the Philadelphia variant (GALKP), which is common in blacks and rare in whites. The frequency of heterozygotes (GALKG/GALKA, GALKG/GALKP) for GALK galactosemia observed in this sample is 1/340 for the total, 1/347 for blacks, and 1/309 for whites. The existence of the GALKP variant allele has been considered in this determination. However, because a method for distinguishing the GALKP and GALKG alleles became available only in the latter part of the study, the frequency of the GALK G allele in the black population may be underestimated. The mean RBC GALT activity for blacks is higher than that for whites, a difference that may be due to a higher frequency of the Duarte variant allele GALTD in whites. Heterozygotes (GALTG/GALTA) for GALT galactosemia were distinguished by family studies and starch gel electrophoresis from individuals who have half-normal RBC GALT activity due to the GALTD allele. The GALTG/GALTA frequency is 1/212 for the total, 1/217 for blacks, and 1/206 for whites. Of the 1,700 individuals surveyed three had atypically high RBC GALK activity, similar to that found in red blood cells of newborns.