Ara-c entrapped into multilamella vesicles (MLV's) composed of PC:C (2:1) (phosphotidylcholine, cholesterol) or PC:SM (1:4) (sphingomyelin) was incubated in the simple salt medium at 37 degrees C for one hour. Its leakage from the liposomes was 5.6-17.6% but, in the presence of serum, the leakage was 35.7-49.1%. Having been incubated at 37 degrees C overnight, the leakage significantly increased but the leakage rate was the highest within the 1st hour. When ara-c entrapped into reverse evaporation vesicles (REV's) composed of PC:C (2:1) or PC:SM (1:4) was incubated in the simple salt medium at 37 degrees C for one hour, its leakage was 2.4-4.1% but, in the presence of serum, the leakage was 10.9-8.2%. When the liposomes were incubated at 37 degrees C overnight, the leakage gradually increased. Whether in the presence of serum or not, the leakage from REV's was much less than that from MLV's. There was no effect on the survival of L1210 leukemia mice when free ara-c was injected intraperitoneally once at the dose of 10 mg/kg, but when the same dose was given for five times, the increase rate in life span was 43.2--51.3%. When ara-c, entrapped into MLV's or REV's composed of PC:C (2:1) and PC:SM (1:4), was given at the dose of 10 mg/kg only once, the effect of intraperitoneal injection was more marked than that of intravenous injection. No effect was observed when free ara-c was continuously infused at the dose of 2 mg/kg once everyday for five days.(ABSTRACT TRUNCATED AT 250 WORDS)