The activity of deoxythymidine kinase was assayed in implanted sponge connective tissue in three groups of subjects: 1) five normal controls (having normal levels of plasma and red cell zinc); 2) four patients with sickle cell anemia who had low zinc in red cells and hair; and 3) two volunteers (under strict dietary controls), after 6 mo of zinc restriction (2.7 mg/day) and repeated after 3 mo of zinc repletion (30 mg/day). Total protein, total collagen, RNA/DNA, and deoxythymidine kinase activity were measured by techniques reported previously. In sickle cell anemia patients, deoxythymidine kinase activity was not detected, and RNA/DNA, total collagen, and total protein contents were decreased compared to normal controls (statistically significant). In human volunteers deoxythymidine kinase activity was not detected during the zinc restriction phase. After supplementation with zinc, deoxythymidine kinase activity became 70% of normal control levels, and RNA/DNA, total collagen, and total protein contents of sponge connective tissue increased. In conclusion, an adverse effect of zinc deficiency on deoxythymidine kinase activity of implanted sponge connective tissue of man has been demonstrated for the first time.