A pair of siblings with analbuminemia were followed for 38 years. The female patient received replacement therapy with human serum albumin. Extreme lipodystrophy developed in this patient by the fourth decade of life. She had juvenile osteoporosis, which normalized under albumin replacement. She died from a granulosa cell cancer at age 69. Her brother never received albumin, even though his serum contained only 60 micrograms/ml of an albumin-like protein. He suffered from severe osteoporosis with gibbus formation, and he died from a colon carcinoma at age 59. Despite high cholesterol values and high levels of several blood clotting factors, neither of the patients had severe atherosclerosis or thrombotic events. Laboratory findings before and after infusion of large amounts of albumin into the sister point to a mechanism whereby albumin-bound substances can be passively transported from the bloodstream into the extravascular space and vice versa.