A strong association has been reported between atherosclerotic diseases and fibrinogen levels, and a decreased whole body protein synthesis has also been reported with aging. We investigated the effect of age on fractional synthesis rates (FSR) of fibrinogen and albumin in 12 human subjects of young (20-30 yr), middle (45-60 yr), and old (65-79 yr) age by use of L-[1-13C]leucine and L-[15N]phenylalanine as tracers. An age-related decline in FSR of fibrinogen (P < 0.01) was observed with use of both tracers, with the maximal decrease (average 37% with alpha-[13C]ketoisocaproate as the precursor) occurring by middle age and with no further changes thereafter. In contrast, plasma concentrations of fibrinogen increased with age (P < 0.002). There was no age-related change in synthesis rate and concentrations of albumin. An age-related decline in fibrinogen FSR, but not FSR of albumin, indicates a differential effect of age on synthesis rate of these two liver proteins. This study also demonstrated that the increased circulating levels of fibrinogen represent a slower rate of disposal of fibrinogen rather than an increased production rate.