1. Cyclosporin A absorption was examined after the instillation of approximately 2 mg/kg into four segments (mean length 15 cm) of rat small bowel, isolated in situ in fed Wistar female rats: SI (duodenum and proximal jejunum distal to the common bile duct); SII (distal jejunum); SIII (proximal ileum) and SIV (distal ileum).

2. Cyclosporin A concentrations in whole blood were assayed by an enzyme-mediated immunoassay for up to 4 h in samples drawn from the femoral vein and used to determine the following pharmacokinetic parameters: the area under the blood cyclosporin A concentration versus time curve (AUC, 0–4 h), the maximum blood concentration of cyclosporin A (Cmax.), the time to reach Cmax. (tmax.), the absorption half-life (t1/2a), the elimination half-life (t1/2λ), and the mean residence time (MRT).

3. Cyclosporin A absorption in SI (AUC, 991 μ l−1 h) was nearly double that in more distal segments and decreased progressively (SII, 533 μg l−1 h; SIII, 470 μg l−1 h; SIV, 419 μg l−1 h). There were corresponding differences in Cmax: 327 μg/l in SI and 201 μg/l, 169 μg/l and 151 μg/l in SII, SIII and SIV, respectively. Tmax. was shorter in SIV (0.9 h) than in other segments (1.3-1.5 h), but there were no significant differences between the segments for t1/2a, t1/2λ or MRT.

4. In the presence of continuous bile flow (diverted via a cannula for SIV), cyclosporin A absorption significantly increased by 23% in SI and by 50% in SIV, but the differential between absorption in SI and SIV was maintained.

5. We conclude that cyclosporin A is absorbed throughout the rat small intestine with the greatest absorption rate in the proximal duodenum and jejunum, and that bile significantly augments cyclosporin A absorption in both the proximal and particularly the distal small bowel.

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