HER2/ERBB2 protein is a 185 kDa transmembrane growth factor receptor whose extracellular domain, a 105 kDa fragment (p105), can be released from cell surfaces by proteolytic cleavage. The aim of our study was to compare serum p105 concentrations in normal and pathological pregnancies and to determine whether any correlation exists between preeclampsia and p105 levels. Serum p105 was assayed in 96 non-pregnant women and 89 pregnant women (26 normotensive, 14 normotensive with a history of preeclampsia or fetal hypotrophy, 10 with chronic hypertension, 10 with gestational hypertension and 29 with preeclampsia). Median serum p105 levels (median; 95% confidence interval) were higher in the preeclampsia group (13.9 microg/l; 12.8-16.1 microg/l) than in the normotensive (11.7 microg/l; 10.6-13.3 microg/l; p < 0.05) or non-pregnant groups (9.3 microg/l; 8.9-9.6 microg/l; p < 0.001). There were no significant differences between the other pregnancy groups. In the normotensive group, serum p105 was correlated with the number of gestations (r = 0.46; p < 0.05), parity (r = 0.39; p < 0.05) and placenta weight (r = 0.61; p < 0.05). In preeclamptic women, serum p105 correlated with parity (r = 0.46; p < 0.05). Serum p105 concentrations above 11.9 microg/l were associated with a high odds ratio (OR) for onset of preeclampsia (after adjustment for parity OR = 9.0; 95% CI = 2.3-36.0; p < 0.005). Preeclampsia is associated with increased serum p105 concentrations, which may be related to increased fetomaternal cell traffic.