The in-vitro activity of SCH39304, a new imidazole, was compared with that of amphotericin B using two media (Sabouraud dextrose and tissue culture (TC) medium) with or without 25% human serum. At an inoculum of 1.5 X 10(4) cfu/ml, the IC95% for amphotericin B ranged from 0.08 to 0.3 mg/l irrespective of the medium. At the same inoculum, the IC95% of the two imidazoles ranged from 0.3 to greater than 80 mg/l. The inoculum effect (from 1.5 X 10(4) to 1.5 X 10(5) cfu/ml) was less than 1 dilution for the three antifungal agents. Serum increased the inhibitory activity (IC80%) of SCH39304 and fluconazole but not of amphotericin B. The IC80%, IC95% and minimal fungicidal concentration (MFC) for amphotericin B usually ranged within two dilutions. Using kill curve methodology, the initial killing rate (0-4 h) of amphotericin B correlated with concentration (P less than 0.001), and was faster in TC medium than in Sabouraud dextrose (P less than 0.0006). SCH39304 and fluconazole did not produce any significant killing over the range of concentrations tested (0.5-20 mg/l). SCH39304 was similar to fluconazole.