Prenylated protein methyltransferase, an enzyme involved in the post-translational modification of many signalling proteins, has been characterized in a parasitic flagellated protozoan, Leishmania dono ani. The activity of this enzyme was monitored by the methylation of an artificial substrate, an S-prenylated cysteine analogue, with S-adenosyl--[methyl-$H]methionine as methyl donor. More than 85 % of the methyltransferase activity was associated with membranes. The enzyme methylates N-acetyl- Strans,trans-farnesyl--cysteine and N-acetyl-S-all-trans-geranylgeranyl--cysteine, but N-acetyl-S-trans,trans-geranyl--cysteine only very weakly. In contrast with the enzyme from mammals, the leishmanial enzyme had a greater affinity for the farnesylated substrate than for the geranylgeranylated one. Activity in itro