A new series of chemicals comprising eight different 3,4-diphenyl-substituted furan analogs, namely, methyl-3,4-diphenyl-2-furoate, methyl-3,4-diphenyl-5-nitro-2-furoate, 3,4-diphenyl-5-nitro-2-furoic acid, 3,4-diphenyl-5-nitro-2-acetylfuran, 3,4-diphenyl-5-nitro-2-bromoacetylfuran, 2-amino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole, 2-acetyl-amino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole and 2-formyl-amino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole were synthesized and their mutagenic activities tested in Salmonella typhimurium. The structure--activity relationship studies revealed that for mutagenic activity the nitro group is essential and that the potency of activity is greatly altered by the nature of the substituent at the 2-position of the furan ring. The mutagenic activities of these chemicals were generally much higher in TA100 compared to TA98. The relative order of activities for 2-substituted, 3,4-diphenyl-5-nitrofurans were COOCH3 greater than COCH2BR greater than COCH3 greater than COOH in S. typhimurium TA100. 3,4-Diphenyl-5-nitro-2-bromoacetylfuran was equally active in nitroreductase-proficient (TA98, TA100) and in nitroreductase-deficient (TA98NR, TA100NR) strains. In contrast, the acetyl and carboxymethyl ester analogs were relatively less active in nitroreductase-deficient strains. Mutagenic activities of 3,4-diphenyl-substituted furylthiazoles in comparison with the unsubstituted analogs of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide, N-[4-(5-nitro-2-furyl)-2-thiazolyl]-acetamide and 2-amino-4-(5-nitro-2-furyl)thiazole revealed that the phenyl groups drastically reduced their mutagenic activities. However, the relative order of activities formylamino greater than or equal to acetylamino greater than amino were the were the same between phenyl-substituted and unsubstituted analogs.