The antibacterial effect of zidovudine (AZT) has been demonstrated both in vitro and in vivo with experimental models of gram-negative bacterial infections. It has been associated with the absence or low occurrence of nontyphoid Salmonella infections in AIDS patients treated with AZT. Using the macrophage cell line J774-2, we demonstrate the inhibition of intracellular growth of Salmonella typhimurium by AZT. This effect is obtained with one-half of the MIC (1 microgram/ml) of AZT for S. typhimurium. Inhibition of intracellular growth is observed after 4 h of incubation and persists at 24 h. Maximal inhibition is shown at a concentration of 128 micrograms/ml, and no further effect is observed with higher concentrations. When the inhibitory effect of AZT is compared with that of pefloxacin or that of ceftriaxone at half their MICs (0.2 and 0.02 microgram/ml, respectively), AZT and pefloxacin give better results than ceftriaxone. In this study, using an intracellular model, we show that AZT is able to inhibit the intracellular multiplication of S. typhimurium at a minimal effective concentration lower than the MIC, indicating its potential for antibacterial accumulation in the macrophages.