A humoral ouabain-like plasma factor has been observed in patients with essential hypertension (EHT). In the present study, we hypothesized that this humoral factor might be responsible for the elevated cytosolic free calcium concentrations [Ca2+]i seen in these patients. Patients with mild to moderate EHT and their normotensive first degree blood relatives (NTBR) participated in the study. Platelet Na+, K+-ATPase activity was assayed in EHT patients and their NT first-degree relatives. To confirm the ouabain-like activity in plasma from EHT patients, control platelets were incubated with EHT and NTBR plasma and their Na+, K+-ATPase activity was measured. In addition, the effect of EHT plasma on platelet45Ca-uptake was studied. Thein vitro effects of ouabain (10 ΜM) on (i)45Ca-uptake and (ii) [Ca2+]i response in control platelets were also observed. A decreased Na+K+-ATPase activity (P< 0.05) was observed in platelet membranes from EHT patients. Incubation of control platelets with EHT plasma decreased their Na+, K+-ATPase activity (P< 0.01) and increased their45Ca-uptake (P< 0.05). C-18 Sep-Pak filtered hypertensive plasma extracts (containing the ouabain-like fraction) also decreased Na+, K+-ATPase activity (P< 001) in control platelet membranes.In vitro incubation of control platelets with ouabain increased45Ca-uptake (P< 005) and [Ca2+]i response (P< 0.05) in these platelets. Thus it appears that an ouabain-like factor in the EHT plasma may contribute to the elevated platelet [Ca2+]i observed in EHT patients.