The cellular effects of three nitrosourea derivatives were investigated on a human lymphoma cell line. The three drugs show similar threshold-type dose-response survival curves on asynchronous cells treated for 1 hr. Longer incubation periods result in rapid biological degradation for 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, whereas, 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea, remains cytotoxic after about 24 hr. Important differences were noted with respect to cell cycle dependency. The 1,3-bis(2-chloroethyl)-1-nitrosourea was more effective in early S and in G2 phase, whereas both 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea were more effective in early S. 1,3-bis(2-chlrorethyl)-1-nitrosourea exerted a considerable degree of killing in G1. Cells were unable to recover from priming damage induced by all 3 nitrosourea derivatives. No synergistic effects were observed in combination with vitamin A.