We investigated the effect of donor pretreatment with chlorpromazine (CPZ), in rabbit livers cold-stored in University of Wisconsin (UW) cold storage solution for 48 hr. Three groups of livers were investigated: livers flushed with Perfadex and immediately thereafter re-perfused on an isolated circuit (controls), and livers cold stored in UW solution for 48 hr, with or without donor pretreatment with CPZ, 3 mg/kg. After preservation, reperfusion was performed in vitro, using an isolated circuit (IPL). The reperfusion medium consisted of an oxygenated Krebs-Henseleit bicarbonate solution supplemented with 5 mM glucose, 50 mg/L of streptomycin and penicillin G, and 3.5% Dextran 60 for oncotic support. Livers that were not pretreated with CPZ produced 5.3±1.2 ml bile/100 g (mean ± SD) during 2 hr of IPL reperfusion. CPZ donor pretreatment significantly improved the bile flow to 17.1±6.9 ml (P<0.01, Wilcoxon). This figure was not different from that in control livers without a storage period (18.3±3.8 ml). Alanine aspartate aminotransferase (ASAT) released into the perfusate was measured, and levels were increasing during 2 hr of reperfusion. ASAT values were moderately increased in the preserved groups compared with controls (P<0.01), with no discernible differences between livers with and without CPZ pretreatment. It is concluded that CPZ pretreatment of the donor improves preservation quality, as evidenced by improved bile formation. The present results suggest that 48 hr cold storage in UW solution may be safe for clinical preservation, if donors are pretreated with chlorpromazine.