In vivo fluorescence microscopy was used for experimental studies of the renal cortical microcirculation in normal mice and in mice pretreated with the nephrotoxic drug cyclosporin A. The cortical circulation was studied after i.v. infusions of a nonionic low osmolar contrast medium (iohexol) and after infusions of mannitol. All infusions produced marked effects on the distribution and velocity of cortical blood flow with no differences between iohexol and mannitol. The renal cortical blood flow was inhomogeneous regarding different capillaries and there was an initial rise in the number of capillaries with increased blood flow after infusions of both mannitol and iohexol. There was simultaneously an increased number of capillaries with decreased blood flow following all infusions. The decreased blood flow after infusion of iohexol was more pronounced when the animals had been pretreated with cyclosporin A. The difference was only significant (p < 0.05) during a short part of the observation period of 30 min, but it may indicate that kidneys previously exposed to cyclosporin A are more susceptible to infusions of iohexol.