Uptake of the nitric oxide synthase inhibitors N-G-methyl-L-arginine (L-NMA) and N-G-nitro-L-arginine (L-NNA) by macrophages is mediated by two different mechanisms. Activation of the cells with cytokines resulted in an up-regulation of L-NMA uptake but did not affect L-NNA transport. Characterization of the transport sites revealed that uptake of L-NMA is mediated by a cationic amino acid transporter (system y(+)) whereas a neutral amino acid transporter (system L) accounts for the uptake of L-NNA.