Interactions between cationic and neutral amino acids in transport across the brush-border membrane, Jmc, of the small intestine have been examined using preparations from the distal rabbit ileum and the rat and guinea-pig mid-small intestine. (1) In the guinea pig, the dependence of Jmc Lys on the concentration of lysine is best described in terms of two saturable transport mechanism in addition to free diffusion. (2) It is shown that the discrepancy between cis-effects of low concentrations of neutral amino acids on the Jmc of cationic amino acids, cis-stimulation in the guinea pig contra cis-inhibition in the rabbit and rat, represents species differences. In the guinea pig, imposing sodium-free conditions turns cis-stimulation into cis-inhibition. (3) It is demonstrated that in rat and guinea pig, leucine is transported both by the transport system(s) for cationic amino acids and by transport system(s) which cannot be inhibited by cationic amino acids.