Human plasma contains hydroxyproline in a bound form that is nondialyzable, is precipitable with the usual protein precipitants, can be extracted with hot trichloroacetic acid, and is released on hydrolysis in 6N HCI. These properties resemble those of collagen and suggest that small amounts of this connective tissue protein (3 to 5 mg per 100 ml), or a very large peptide derived from it, normally circulate in the blood. The identification and analysis of hydroxyproline in hydrolyzates of plasma protein were based on isotope-dilution procedures.