Influences of age (3 wk, 2, 7, 19, or 26 mo), long-term dietary restriction (DR) started at 3 wk of age, and acute fasting state on serum thymosin alpha 1 (T alpha 1) levels were measured by radioimmunoassay in female mice from a long-lived strain. The average T alpha 1 level was highest (approximately 60 ng/ml) at 3 wk and fell sharply such that 2 mo old mice fed either normal (N, approximately 80% of ad libitum intake) or restricted (R, approximately 50% of ad libitum intake) diets averaged approximately 20 ng/ml. Any age-related declines after 2 mo of age were mild and statistically significant only for R mice bled 2-4 h (but not 24-48 h) post-feeding. T alpha 1 levels were lower in group R than in group N mice in one experiment at 19 mo of age but not in another at 26 mo. The decline with age in serum T alpha 1 levels is mainly a very early life event for mice of this hybrid strain and appears uninfluenced by DR. T alpha 1 levels are variably reduced by DR later in life.