We investigated the components of biological variation, including seasonality, in plasma haptoglobin (Hp) levels and the relationships between plasma Hp and interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6), sIL-2R, fibrinogen (Fb) and absolute number of peripheral blood mononuclear cells, such as leukocytes, neutrophils, monocytes, lymphocytes, CD4+, CD8+, CD25+ T cells and CD20+ B cells. Monthly blood samples were taken from 26 normal volunteers during one calendar year. The estimated inter- and intra-individual C.V. values for plasma Hp were 27.9% and 20.0%, respectively; the index of individuality was 0.72. No significant seasonal rhythms could be detected in plasma Hp levels. The yearly mean values in plasma Hp were significantly and positively related to those in plasma Fb, absolute number of leukocytes, neutrophils, CD4+ T cells and the CD4+/CD8+ T cell ratio. 49.0% of the variance in the yearly mean values of plasma Hp could be explained by variances in serum IL-6 and number of CD4+ (positively related) and CD8+ (negatively related) T cells. There were significant and positive time relationships between plasma Hp, on the one hand, and plasma Fb, sIL-6R, sIL-2R and number of leukocytes, neutrophils and monocytes, on the other. A smaller part of the within-subject variability in plasma Hp (i.e. 6.0%) could be explained by serum sIL-6R and sIL-2R. It is concluded that there are (1) important between-subject differences in the homeostatic setpoints of plasma Hp, which are related to those in plasma Fb and in immune status and (2) significant within-subject, time relationships between plasma Hp and indicators of immune activation and plasma Fb.