The possible between macrophages and fluconazole for antifungal activity against different isolates of C. albicans was studied. The susceptibility of C. albicans isolates to fluconazole (FCZ), when incubated in RPMI-1640 with 10% fetal bovine serum (FBS) and 10% fresh mouse serum (test medium, TM) was determined by using a quantitative culture methodology, Multiplication of isolate Sh27 was strongly inhibited by FCZ, even at 1.0 microgram/ml. However, FCZ even at 100 microgram/ml was not fungicidal. Resident murine peritoneal macrophages (MP) incubated for 48 h in RPMI-1640 + 10% FBS (tissue culture medium, TCM), then challenged with Sh27 in TM for 24 h, were fungistatic (20 +/ 9%, n = 4). Cultured macrophages synergized with FCZ (10 micrograms/ml) for fungicidal activity when co-cultured with sh27 in TM for 24 h (46 +/ 8%) and for 48 h (74 +/ 5%), n = 3. Macrophages and FCZ (10 micrograms/ml) could not synergize for significant killing of a less FCZ-sensitive C. albicans isolate 94-164. Multiplication of a FCZ-resistant isolate (94-20) was not inhibited by FCZ at 10 micrograms/ml TM; however, macrophages and FCZ (10 micrograms/ml) could synergize for fungistatic (64%), but not fungicidal, activity.