The single dose intravenous pharmacokinetics of talisomycin (3 mg/M2) and bleomycin (18 U/M2) were determined in the rhesus monkey at non-nephrotoxic doses. Serum concentrations were analyzed by radioimmunoassay procedures. The tissue distribution of talisomycin was significantly higher and the elimination slower than bleomycin. The volume of distribution (Vdss) was 2.3 and 22.6 L/M2 for bleomycin and talisomycin, respectively. The volume of the peripheral tissue compartment (V2) of talisomycin was 17 times greater than bleomycin. The slower elimination of talisomycin was reflected by a half-life (t1/2) of 10.6 hr versus 1.6 hr for bleomycin. The slower elimination from the peripheral tissue compartments was also evidenced by a five-fold difference in the tissue transfer ratio (k12/k21) for these compounds. Similar differences, of lesser magnitude, have also been reported in the dog. The potential for higher tissue distribution and slower elimination of talisomycin could be related to the differences in in vivo antitumor activity and toxicity, and should be considered in design of the dose schedule in clinical studies.