Precision-cut liver slices (PCLS) preserve the tissular organization of the organ and represent an in vitro model closer to in vivo conditions than hepatocytes cultures. As this may be an interesting tool not only for the investigation of hepatotoxic and protective effects but also for bioguided fractionations schemes, the usefulness of PCLS was compared with an in vivo test of liver function. Crude extracts derived from five herbs used in Rwanda for hepatoprotective activity were tested on CCl(4)-treated guinea pigs by the method of barbiturate-induced sleep modification. Aqueous extracts of Ocimum lamiifolium, Crassocephalum vitellinum, Guizotia scabra and Vernonia lasiopus leaves allowed animals to recover barbiturate sleep duration in proportions of 88%, 78%, 61% and 34%, respectively and Microglossa pyrifolia was found inactive. Dried methanolic extracts of the 5 plants were then tested in vitro on rat PCLS for protection against acetaminophen-induced hepatotoxicity. In this model, G. scabra, M. pyrifolia and V. lasiopus were found hepatotoxic by themselves and unable to prevent acetaminophen toxicity. The most active extract, obtained from O. lamiifolium, was subjected to bioassay-guided fractionation by chromatography on Si-C(18) to yield two quite active fractions. From a single animal, at least 50 PCLS explants can be prepared, which allows testing large amounts of samples, strengthening ethnopharmacological data on hepatoprotective medicinal plants and investigating hepatotoxic effects.