It has been demonstrated in vitro that lipoprotein(a) [Lp(a)] increases the endothelial synthesis of plasminogen activator inhibitor 1 (PAI-1). However, this effect in vivo is controversial, and the possible relationship between PAI-1 and Lp(a) phenotypes has not been evaluated. The aim of the study was to determine the influence of Lp(a) and its phenotypes on PAI-1 serum concentrations in diabetic patients. For this purpose we include 75 Caucasian diabetic patients (34 consecutive type I and 41 consecutive type II) without late diabetic complications. Lp(a) and PAI-1 were assessed by ELISA. Lp(a) phenotypes were determined by SDS-PAGE followed by immunoblotting, and grouped according to size in small (F,B,S1,S2), big (S3,S4), and null. A linear correlation between Lp(a) and PAI-1 was not observed either as a whole or when type I and type II diabetic patients were analyzed separately. However, significant differences were detected in PAI-1 levels when Lp(a) phenotypes were considered (small: 42.1+/-31.8 ng/mL; big: 37.2+/-26.1 ng/mL; null: 14.4+/-14.4; p< 0.05). The significant differences were due to the low PAI-1 concentrations observed in patients with null phenotype. Our results suggest that fibrinolytic activity might be preserved in diabetic patients with null Lp(a) phenotype. Furthermore, it could be speculated that diabetic patients with null phenotype should be considered at low risk to develop cardiovascular disease.