Recent studies have shown that Nocardia asteroides isolates have five major antibiotic resistance patterns; one of these patterns identifies isolates of Nocardia farcinica. In the current study, we investigated a second pattern characterized by susceptibility to ampicillin and erythromycin. This pattern was seen in 17% of 223 clinical isolates identified by standard techniques as N. asteroides and associated with diseases typical for nocardiae. Biochemically, isolates with this drug pattern were relatively homogeneous and identical to the type strain and previous descriptions of Nocardia nova. The strains studied were unique among nocardiae in having both alpha- and beta-esterase activity (85 and 95%, respectively). However, the arylsulfatase activity at 14 days (75%) and antimicrobial susceptibility patterns, including susceptibility to erythromycin (100%), were the only routinely available methods that would separate N. nova strains from other members of N. asteroides. N. asteroides should be considered a complex because current clinical identification schemes include isolates of N. farcinica and N. nova and may well include additional species. This is the first detailed description of N. nova as a pathogen in humans.