The disposition of primaquine (0.75 mg, 5 pC1) has been investigated in the isolated perfused rat liver (IPRL) preparation alone and concurrently with mefloquine. In both groups, primaquine concentrations declined exponentially. There were no significant differences between the respective groups in the half-lives (2-5 f 1-5, 2.2 f 1.1 h), AUCs (0.43 f 0.14, 0.372 f 0.096wghml-'), clearances (19.0 f 5.4, 21.1 f 4.2 rnl h-I), and apparent volume of distribution (78.9 f 28-1, 76.2 f 31.7ml). In the presence of mefloquine, total bile production was significantly reduced (1244.5 f 317.1 111) compared with primaquine alone (1621.5 f 174.2 111). Hence, although significantly less radioactivity (['HI) was eliminated in bile in the presence of mefloquine (30.0 ?r 7.9 per cent versus 39.9 2 3.6 per cent) there was no significant difference between the groups in ['H]/pl bile eliminated. Significantly more ['HI was recovered from the livers of the mefloquine/ primaquine group. This was underlined by the significantly greater proportions of ['HI recovered from the 10000 g pellet, 10000 g supernatant and 105000 g supernatant in the presence of mefloquine compared with primaquine alone. Hence, it appears mefloquine had little or no direct action or primaquine metabolism, but significantly reduced bile production.