We have studied the disposition of bleomycin, melphalan, or vinblastine after intraperitoneal (IP) instillation in 14 cancer patients. Although IP bleomycin had a somewhat longer terminal-phase plasma half-life than after intravenous (IV) administration (5.5 vs 4.0 h, respectively), its systemic absorption averaged only 44%-52% of the administered dose. IP melphalan's mean terminal-phase half-life of 1.3 h was similar to that seen after IV drug administration. Melphalan's systemic absorption form the IP space averaged only 39% of the administered dose. In contrast, vinblastine plasma levels remained elevated for longer than 24 h after IP instillation. Its use was associated with life-threatening adynamic ileus in two patients. Bleomycin's and melphalan's reduced systemic availability after IP dosing suggests that their dose could be increased safely by a factor of two over their standard IV doses.