Severe DNA damage, which might prevent egg fertilization or the development of the embryo, could be a cause of infertility. In order to assess whether polycyclic aromatic hydrocarbon (PAH)-DNA adducts are an early marker of sperm genotoxicity and infertility, we studied 205 men consecutively recruited from 1 January to 30 May 2001 through the Infertility Clinic of the University of Milan (Italy), with morphological abnormalities in the sperm. No known causes of infertility were present in their female partners. Sperm were collected after 3-5 days of abstinence, fixed on polylysine slides, and frozen at -20 degrees C. PAH-DNA adducts were measured by immunofluorescence using a polyclonal antiserum. A questionnaire was filled out at the time of the visit, with demographic information, smoking and drinking habits, and occupational history. Data on PAH-DNA adducts were available for 182 men. The mean age of the subjects was 35.5+/-5.0 years; 38.6% of them were current smokers. PAH-DNA adducts were negatively correlated with the percentage of physiologic forms (r=-0.18; P=0.016) and with abnormalities of the neck of the sperm cell (r=-0.21; P>/=0.009), while they were positively correlated with morphological abnormalities of the head (r=0.30; P>0.0001). Occupational exposure to PAH, but not smoking, was significantly associated with higher levels of PAH-DNA adducts. A significant negative association was observed between daily alcohol consumption and PAH-DNA adducts in sperm (P=0.01). PAH-DNA adducts levels were significantly higher in infertile versus fertile men (P=0.04). These results suggest a role for DNA damage in infertility.