The transfer rates of lidocaine and five derivatives were measured across the everted rat intestine. No obvious relationship was observed between the first-order rate constants for transfer and the lipophilicity of the compounds as measured by their apparent partition coefficients. The intestinal mucosal epithelium also did not appear to be the rate-limiting barrier for the passage of these agents across the intestinal membrane regardless of the respective clearance of the compound. It is suggested that the ionized form of these agents may be capable of crossing the intestinal barrier at substantial rates, although it is not known if a similar situation exists in vivo. The transfer rate is believed to be due to the passage of intact drug and not the metabolite.