The human plasma protein, alpha 2HS glycoprotein, has an amino acid composition very similar to that of fetuin, the major protein in fetal calf and lamb serum. Immunohistochemical studies of human fetuses (6-33 weeks gestation) showed that alpha 2HS glycoprotein and fetuin have similar distributions in developing brain and several other tissues, e.g., bone, kidney, gonads, gastrointestinal tract, respiratory and cardiovascular systems. There were notable differences in the liver and thymus in the distribution of the two proteins. Fetuin and alpha 2HS glycoprotein are present in plasma and cerebrospinal fluid of both human and sheep fetuses; their concentrations are reciprocally related: in human plasma and cerebrospinal fluid alpha 2HS glycoprotein concentration is high and fetuin low; the reverse is the case in sheep fetuses. Estimates of the concentration of alpha 2HS glycoprotein in human fetal cerebrospinal fluid and plasma were obtained. It is suggested that alpha 2HS glycoprotein may play a role in developing tissues, especially in the human fetus, similar to that of fetuin in other species.