Considering the necessity to monitor rainwater quality and the limited existing data regarding wet precipitations' toxic potential, the toxic potential of rainwater (RW) samples collected in three cities of Western Greece (Corfu, Agrinion and Patras) during May, October, November, and December of 2014 were investigated. The relationship of the adverse effects obtained, against cytokinesis block micronucleus (CBMN) and Vibrio fischeri bioluminescence (Microtox) assays with the physicochemical characteristics, the heavy metal concentration levels of rainwater samples and the meteorological parameters governing the climatic conditions in each region, were studied in detail. All samples showed pH values in the range of 5.37-7.17, high concentrations of ΝΗ4+ and the presence of SO42- and NO3-. The metals Al, Mn, Fe, Co, Ni, Cu, Zn, As, Sb, Cd, were detected in most of the samples, with maximum concentrations ranging from 0.16 μg L-1 (for Co) to 86.6 μg L-1 (for Fe). The CBMN assay showed statistically significant rainwater cytotoxic activity at 5% (v/v) concentration in all cities during all months studied and at 10% (v/v) in Agrinion and Corfu in May. No genotoxic effect was induced at 5% (v/v) concentration of rainwater, except for Corfu city during November, whereas 10% (v/v) of rainwater led to statistically significant increase in micronuclei frequencies in all three cities. The highest (100%) and the lowest (14%) inhibitory effect exhibited by the rainwater in the Vibrio test were noticed at Corfu city during May and December, respectively. Considering the inter-relations obtained among the abiotic and biotic variables measured in all cases, conductivity, SO42-, NH4+, and total metal burden could be related with both CBMN and Microtox assays data, regardless of the site- and month-specific differences. The multidisciplinary approach presented here showed that the physicochemical profile of rainwater precipitation could be significantly related with the induction of adverse effects on biota.