We studied in mice the in vivo pharmacokinetics and toxicity of murine monoclonal antibodies (MCA) and of disulfide-linked MCA conjugates of gelonin, a ribosomal inhibitor prepared from the seeds of Gelonium multiflorum. Iodinated MCA with specificity for human determinants and of gamma 1 or gamma 2a isotype had a circulatory half life (T 1/2) in the mouse of 4 days, which is consistent with previously published estimates of the circulatory T 1/2 of heterogeneous murine IgG. Iodinated murine MCA with specificity for murine determinants had a much shorter T 1/2, probably reflecting antigen binding. This effect could be partially overcome by the simultaneous injection of unlabeled MCA of identical specificity. Clearance of MCA-gelonin conjugates was characterized by an initial rapid phase lasting 8-12 h with a T 1/2 or from 4 to 7 h, followed by a slower clearance phase with T 1/2 approaching that of MCA. Moreover, the presence of significant amounts of intact conjugate in the murine circulation was demonstrable, by SDS gel electrophoresis, for up to 48 h post injection. Intraperitoneal injection of MCA-gelonin conjugate resulted in circulating levels identical to those achieved after i.v. administration after an initial 4 h equilibration. The LD50 of MCA-gelonin conjugates was approximately 25 mg/kg (i.v.) while that of gelonin was approximately 75 mg/kg (i.v.) MCA alone showed no toxicity in doses in excess of 150 mg/kg. At doses below the LD50 immunoconjugates caused a dose-dependent reversible weight loss. The main site of toxicity of MCA-gelonin conjugates was the liver; histopathological examination revealed dose-dependent foci of necrosis and acute inflammation. No pathology was observed in lung, spleen, kidney, gut or brain. The relationship to previous work in this area is discussed.