With the aim of examining the possible basis to i.p. urethane anaesthesia-induced reductions in renal clearance, this study has investigated: (a) the influence that some anaesthetic regimens may have on the renin-angiotensin system (RAS); and (b) the ability of these anaesthetic regimens to initiate intraperitoneal toxicity. In the rat, i.p. urethane anaesthesia, compared with pentobaritone i.p. and "Hypnorm/Hypnovel" i.p. anaesthesia, resulted in significantly lower mean arterial pressure (MAP) and elevations in plasma renin activity (PRA) in both surgically-prepared and surgically-intact animals. Urethane anaesthesia also produced intraperitoneal toxicity, which was characterized by a greater peritoneal fluid volume and peritoneal cavity total protein content. The elevated protein content in the peritoneal cavity resulted in part from plasma leakage from the vascular compartment, as demonstrated by i.v. Evans' blue dye studies. Intraperitoneal toxicity was absent following administration of urethane by either i.v. or oral routes. A reduction in systemic perfusion pressure and an elevation in renal vascular resistance, via activation of the RAS are likely to be responsible for i.p. urethane-induced reductions in renal clearance. Intraperitoneal toxicity is likely, only in part, to be responsible for such changes.