We evaluated the clinical profile, outcome and serial plasma interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) concentrations in 38 consecutive children (aged 6 months - 14 years) admitted with culture-proven multidrug-resistant typhoid. All children received therapy for 14 days with either i.v. ceftriaxone or oral cefixime, with comparable outcome. Concentrations of IL-6 and TNF-α were significantly elevated in over 50% of the cases and correlated with clinical severity of illness as quantitated by the typhoid morbidity score. Sequential measurements revealed a significant decrease in IL-6 and TNF-α concentrations within 7 days of initiation of therapy (P < 0.05). While no clear relationship was seen with time-to-defervescence, the failure rate was significantly higher in children with baseline serum IL-6 values > 400 pg/ml (P < 0.05). Our data suggest that plasma cytokine activity is frequently elevated in children with typhoidal salmonellosis, and IL-6 concentrations show a correlation with clinical severity and recovery from the illness.