The relative importance of peak level- and residual level-related flukicidal activity of closantel against immature and mature Fasciola hepatica was evaluated in a comparative efficacy trial using two animal species with a different plasma elimination pattern, that is, the rat and the sheep with an elimination half-life of less than one week and of two to three weeks, respectively. The rats were dosed orally with closantel at 20 mg kg-1 at two, four, six, eight and 10 weeks; the sheep at 10 mg kg-1 at eight, 10 and 12 weeks after artificial infection. Necropsy was performed either one week after treatment or 12 weeks after infection. Efficacy rates and the length of the recovered flukes were evaluated. It was demonstrated that the flukicidal effect of closantel is directly related to its peak plasma levels and less to its residual plasma concentrations. In the rat, a high efficacy (P less than 0.001) could be demonstrated against immature stages of four weeks or older. The two-week immature stages were less markedly affected. No significant differences in efficacy and size of the flukes were noted between the animals autopsied one week after treatment and those autopsied 12 weeks after infection. In the sheep, the efficacy against six-week and eight-week-old immature stages varied between 70.3 and 76.8 per cent and between 92.8 and 96.5 per cent, respectively. As in the rats, no marked differences in efficacy were noted between the animals autopsied one week after treatment and those autopsied 12 weeks after infection.(ABSTRACT TRUNCATED AT 250 WORDS)