Some antibiotics have been shown to modify the host immune response. Infection with Stenotrophomonas maltophilia, is often difficult to treat due to multiresistance to antibiotics. The authors examined the effect of four commonly used antimicrobial agents (ciprofloxacin, ceftazidime, cotrimoxazole and piperacillin-tazobactam) on tumour necrosis factor alpha (TNF alpha) production by human peripheral blood mononuclear cells (PBMC) stimulated with heat-killed S maltophilia. Cotrimoxazole was the only antibiotic that suppressed TNFa secretion at clinically achievable concentrations. This may explain its use with good effect in the treatment of S maltophilia infections. However at supratherapeutic concentrations, ceftazidime and ciprofloxacin, but not piperacillin-tazobactam, also inhibited significantly the production of TNF alpha. Cotrimoxazole, in addition to its antimicrobial effect against S maltophilia, has an immunomodulatory effect on peripheral blood mononuclear cells stimulated by S maltophilia.