A few 1-aryl 3-(2-chloroethyl)ureas (CEU) were synthesized and screened in vitro for their cytotoxicity. Some of these derivatives were assayed for their mutagenicity, their in vivo toxicity and their antineoplastic activity. Methyl 4-(p-(3-(2-chloroethyl) ureido) phenyl) butyrate, 4-methyl and 4-tertbutyl (3-(2-chloroethyl) ureido) phenyl) butyrate, 4-methyl and 4-tert-butyl (3-(2-chloroethyl) ureido) benzene had an ID50 of 28, 20 and 4 microM respectively when tested on LoVo cells, while chlorambucil (CBL) and CCNU had an ID50 of 21 and 45 microM. These 3 chloroethyl urea derivatives were not toxic when injected i.p. at doses up to 220 mg/kg, whereas chlorambucil was already toxic at 18.5 mg/kg. The survival time of BDF1 mice bearing L1210 leukemia tumors was significantly enhanced by intraperitoneal injections of CBL and CEU. The most cytotoxic derivative (tert-butyl derivative) gave the best antineoplastic activity with a median survival time 1.77 times that of the control at 10 mg/kg/day and was not toxic, whereas CBL at this concentration enhanced survival time by a factor of 1.6 and presented important side effects. The 4-tert-butyl (3-(2-chloroethyl) ureido) benzene and the methyl 4-(p-(3-(2-chloroethyl) ureido) phenyl) butyrate showed no mutagenicity when assayed on TA-97, TA-98, TA-100 and TA-102, four strains of S. thyphimurium, while CBL had a weak effect on TA-102 and CCNU was highly mutagenic on TA-100 and TA-102.