The activity in vitro of clarithromycin, a new macrolide, was compared to that of various antibiotics in tests using 3,880 clinical isolates. Clarithromycin was two times more active than erythromycin against Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, streptococci of groups C, G and F, Brucella melitensis, Legionella pneumophila and Mycoplasma spp., 16 times more active against Ureaplasma urealyticum and 2 to 4 times less active against Campylobacter spp. In general, clarithromycin showed intrinsic activity 2 to 4 times higher than that of roxithromycin and 4 to 8 times higher than that of miocamycin. Cross-resistance was found between the macrolides. Clarithromycin was bactericidal against Streptococcus spp. and Haemophilus influenzae.