We studied the role of blood-dialyzer-membrane interactions in hemodialysis-induced hypoxemia by measuring PaO2 and white blood cell counts during isolated ultrafiltration (UF). These values were compared to those obtained from the same patients during subsequent hemodialysis (HD; utilizing the same dialyzer and membrane). Patients in the UF period displayed no hypoxemia, rather a slight increase in PaO2 (from 82.5 ± 3.0 to 88.5 ± 2.0 mm Hg, mean ± 0.05). In contrast, these patients displayed significant hypoxemia when HD was imposed (88.5 ± 2.0–78.0 ± 1.5 mm Hg, mean ± SE, p < 0.02). We suggest that the hypoxemia characteristic of HD initiation is not solely dependent on blood-dialyzer-membrane interactions, but also requires blood-dialysate inter