The cytotoxicity of a new compound, sarcosinamide chloroethylnitrosourea (SarCNU), was compared with that of the clinically available bis-chloroethylnitrosourea (BCNU) in 13 primary human gliomas and in 3 human glioma cell lines using the Human Tumor Cloning Assay (HTCA). At concentrations less than or equal to 16 micrograms/ml, SarCNU reduced the growth to less than or equal to 30% of control in 11 of 13 primary gliomas. At similar concentrations, BCNU produced a comparable cytotoxic effect in 6 out of 13 specimens. At concentrations less than or equal to 16 micrograms/ml, BCNU reduced colony growth to less than or equal to 30% of control in all three glioma cell lines and SarCNU produced the same effect in only one glioma cell line. A recently described statistical model, which employs the LD50 dose of new agents in mice, was used to estimate the achievable peak plasma concentration (PPC) of SarCNU. The calculated PPC for SarCNU was found to be 14.8 micrograms/ml compared with 2 micrograms#ml for BCNU. A reevaluation of the cytotoxic activities of SarCNU and BCNU at concentrations approximating their respective PPCs revealed that SarCNU reduced the growth to less than or equal to 30% of control in one cell line at a concentration below its PPC. In contrast, BCNU exhibited similar toxicity in each cell line only at concentrations exceeding its PPC of 2 micrograms/ml. In the case of the primary gliomas, SarCNU was active (less than or equal to 30% of control) in ten tumors at concentrations less than or equal to 14.8 micrograms/ml, whereas BCNU was active in only one glioma at a concentration less than or equal to 2 micrograms/ml. The results suggest that SarCNU should be more active than BCNU against human gliomas, provided that the statistical model used has correctly estimated the PPC of SarCNU.