A study of the in-vitro activity of RP 59500, a semi synthetic derivative of pristina- mycin, against a range of Gram-positive bacteria including erythromycin-resistant strains was undertaken. MICs were determined by plate dilution in IsoSensitest agar and MBCs by velvet pad replication. RP 59500 was found to have in-vitro activity almost identical to that of its parent compound, pristinamycin. Sixty methicillin- resistant Staphylococcus aureus (MRSA) and 60 methicillin-sensitive 5. aureus (MSSA) were found to be sensitive to RP 59500, with MICs of 0.13-1 mg/L. All the MSSA and most MRSA showed an MBC < 2 mg/L. Erythromycin-resistant S. aureus (62) were as sensitive to RP 59500 as were erythromycin-sensitive strains (58). RP 59500 was more active against MRSA than fusidate, vancomycin, ami-kacin, dprofloxacin, imipenem or erythromycin. Forty strains of coagulase-negative staphylococd (11 were erythromycin-resistant) showed MICs of 0.25-1 mg/L, and RP 59500 was more active than methicillin, erythromycin, imipenem, cefotaxime or vancomycin. Sixty strains of streptococci (20 pneumococci and 40 of groups A, B, C, or G) and 20 enterococci were inhibited by 0.13-1 mg/L and 0.25-4 mg/L, respectively. Gram-positive bacilli (five each of diphtheroids, lactobacilli, Listeria monocytogenes and Bacillus spp., and 19 Clostridium spp.) were also sensitive, with MICs of between 006 and 4 mg/L. All 279 strains tested were judged to be sensitive to RP 59500, which was bactericidal and showed a small inoculum effect The activity against MRSA, and against erythromycin-resistant strains of all spedes, was particularly interesting. © 1992 Oxford University Press.