The genotoxic potential of samples from a river basin under impact of agricultural, urban and industrial activities was studied, to investigate the influence of climatic variations on the mutagenicity. Three sites were analyzed, a reference-SI121-and two with strong anthropic influence-SI028 and SI008. The Salmonella/microsome assay was performed in the presence/absence of hepatic metabolic system in samples of water and organic extracts. Different strains were used to identify frameshift mutagens, base-pair substitutions and oxidative damage. Indicative mutagens were detected especially with metabolization. The toxic response, which was quite frequent, may have interfered in the mutagenicity detection. The adverse impact of anthropic activities was detected through recurring cytotoxic and mutagenic responses at the site of greater urban and industrial concentration. The data suggest the influence of climatic conditions on mutagenic response, reinforcing the need to investigate mutagenicity for a prolonged period to a better risk assessment of exposure.