Two tritium-labeled epimers of dihydromicrocystin-LR, a derivative of the cyanobacterial peptide hepatotoxin microcystin-LR, were synthesized by reduction with sodium boro[3H]hydride and purified with reversed-phase liquid chromatography. The epimers were hepatotoxic in mice; the i.p. LD50 was 120-135 micrograms/kg. They were concentrated in the liver and to some extent in the intestine and the kidney after an i.v. injection. Freshly isolated rat hepatocytes showed a rapid uptake of both epimers. The cellular uptake of the epimers was almost complete within 5 min at concentrations 1 microM (0.5 microM dihydromicrocystin-LR + 0.5 microM microcystin-LR) and 4 microM (0.5 microM + 3.5 microM). The uptake of the earlier eluting epimer was about three times higher than that of the later eluting epimer.