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Composite sediment samples were collected from 18 deposition areas located in seven lagoons of the Po Delta. Samples were analysed for contents of legacy (DDT, PCB) and priority organic pollutants (AP, PBDE), and the sediments showed, with some exceptions, low/moderate levels of contamination. It seemed evident that the Po River has a clear role in controlling the input and distribution of chemicals to the lagoons, generally resulting in an overall north-south pattern of increasing contamination, as well as some contaminant contents exceeding quality guidelines or threshold values (NP, PBDE, PCB). Interestingly, more negative δ13C values were observed in the lagoons exposed to freshwater inflows, with higher concentrations of DDTs in their sediments. Regarding potential toxic effects, different sex ratios were observed in Manila clams (Ruditapes philippinarum) previously exposed for 3 months to six lagoons of the Po Delta, and these ratios ranged from a marked male to female prevalence. Notably, the male clam percentage was inversely correlated with sedimentary PCB and partially correlated with PBDE, bioaccumulated PCB, PBDE and to a lesser extent APs and DDTs. A delay in gonad development was also present in the clams most exposed to sedimentary APs and in general to inland waters. For the first time, this study evidenced endocrine disruption in Manila clams exposed to the Po Delta lagoons that was apparently the result of exposure to major contaminant classes. These ecotoxicological results need to be further investigated, in light of the many other endocrine disrupters recently identified in Po lagoons. • PCB, NP and PBDE are ubiquitous in lagoon sediments and ecologically relevant. • Lagoons more exposed to inland water generally show higher levels of contamination. • Delay in gonad development of Manila clam seems to be evident in less marine lagoons. • Male proportion of Manila clams is inversely related to PCB and PBDE exposure levels. [ABSTRACT FROM AUTHOR]