The cardiovascular drug lacidipine (Lc) is known to possess antibacterial activity. Further potentiation of action is possible by synergism between Lc and an antibiotic or a non-antibiotic. The minimum inhibitory concentration (MIC) of antibiotics, Lc and other non-antibiotics were detected by the agar dilution technique in different bacteria. Synergism was determined by disc diffusion assay, the fractional inhibitory concentration (FIC) index through checkerboard assessment and, also, the protective capacity of the combination by administering the drugs along with 50 x LD(50) challenge dose of virulent Salmonella typhimurium in animal experiments. Synergism between Lc and penicillin was found to be statistically significant (P <or= 0.01) when compared with their individual effects. The FIC index of this combination was 0.375, confirming synergism. In vivo tests suggested the statistically significant protection of infected mice with this combination. Lc exhibited synergism when combined with non-antibiotics methdilazine and triflupromazine both in vitro and in vivo. Distinct antimicrobial action of Lc and its subsequent synergism with other drugs can open up the possibility of synthesising new molecules by the structural analyses of these compounds.