Transfer of phenytoin (PHT) across the rat term placenta perfused in situ was investigated and compared with that of antipyrine (AP) as a marker of passive diffusion. PHT was shown to cross the placenta with similar kinetics as AP did. Both the first order transfer constant (ktr = 0.070 min-1) and the first order equilibration constant (keq = 0.027 min-1) of PHT were comparable to those of AP (ktr = 0.046 min-1, keq = 0.022 min-1). Similarly, there were significant differences between PHT and AP in the foeto-maternal concentration ratio at equilibrium (FMCReq = 1.01 and 1.09, respectively). The present data indicate that the transfer of PHT through the rat placenta is governed by the same principles as that of AP, i.e. by the mechanism of passive diffusion. Surprisingly, maternal plasma protein binding of PHT (60.5%) did not seem to influence either its rate of transfer or its eventual foeto-maternal concentration ratio.