A comparative pharmacokinetic study of Lositril (rifampicin) was carried out in six multibacillary and twelve paucibacillary leprosy cases. The type of leprosy had no significant effect on rifampicin pharmacokinetics. The effect of dapsone and clofazimine when given separately and in combination was studied on rifampicin pharmacokinetics in each group of six patients. Within group comparison revealed that clofazimine reduced rifampicin absorption significantly (P less than 0.01) and prolonged the time to reach the peak serum concentration (P less than 0.01). Since MCR and Ke were also reduced significantly in RC group, as compared with RDC group (P less than 0.02 and P less than 0.05 respectively), no significant alteration was seen in overall Auc and Cmax, although t0.05 was increased significantly (P less than 0.02) in RC Group. Dapsone alone did not produce any significant alteration in rifampicin pharmacokinetics parameters, while dapsone with clofazimine reduced rifampicin 1h serum levels (P less than 0.05) and Auc (P less than 0.05) significantly. Of the three groups, except RC group, both RDC and RD groups were homogeneous Ka, avd, Cmax and Auc/t0.5 ratio of RC group were significantly different from those in RD group. While Ka and avd were significantly less (P less than 0.05 and less than 0.001 respectively) and Cmax and Auc/t0.5 ratio were significantly more (P less than 0.01) in RC group. Since clofazimine reduced rifampicin absorption, the difference in Ka and tp became more significant in the post-regimen phase (P less than 0.01).