Objective Pregnancy-associated plasma protein-A (PAPP-A) is a protease promoting IGF1 tissue availability and considered as a new biomarker of cardiovascular disease. Aim To evaluate the relationship between PAPP-A concentrations and anthropometric variables, physical activity, smoking status, glucose homoeostasis and adipocytokines in healthy adults. Design and methods One hundred and forty-nine subjects (77 women; mean age 39·7 ± 14 years; mean BMI 23·7 ± 1·9 kg/m2) were randomly selected from 8000 adults of The Health Survey of Catalonia. Possible effects of gender, age, body composition, smoking status, physical activity, glucose homoeostasis and adipocytokines on PAPP-A concentrations were assessed. Results Pregnancy-associated plasma protein-A was significantly higher in men than in women [â€Š1·04 (0·61-0·44) vs 0·61 (0·41-0·90) μIU/ml; P < 0·0001]; there were no differences in relation to physical activity or smoking status. PAPP-A showed a negative correlation with leptin in men (P = 0·01) and women (P = 0·05), and a positive correlation with adiponectin (P = 0·006) in women and a trend (P = 0·073) in men. Homoeostasis model assessment of insulin resistance (HOMA-IR) showed a negative correlation with PAPP-A only in women (P = 0·019). No association was found with blood pressure, IGF1, lipids or glucose in either gender. When a multiple regression analysis was performed including gender, age, BMI, waist-hip ratio, HOMA-IR, adiponectin and leptin as confounders, PAPP-A was independently correlated with adiponectin (β = 0·23; P = 0·02) and leptin (β = -0·33; P = 0·04). Conclusions Our study shows a sexual dimorphism of PAPP-A, and a possible influence of leptin and adiponectin on its concentrations in healthy subjects. The mechanisms responsible for this relationship remain to be determined. © 2012 Blackwell Publishing Ltd.