Even though it is widely known that interleukin (IL)-1α acts at the local level, it is still uncertain whether IL-1α is secreted into the circulation and acts at distant sites. We have tried to elucidate this by measuring 24-hour levels of total IL-1α in six healthy female volunteers. Subjects had detectable and pulsatile levels of IL-1α throughout the 24-hour period. The integrated 24-hour IL-1α concentration was 2,367 ± 753 min x μg/1 (mean ± SD), and the integrated pulsatile IL-1α concentration was 553 ± 260 (25 ± 10% ot total integrated IL-1α). The mean IL-1α concentration was 1.63 ± 0.53 μg/1, mean pulse frequency/24 h was 12.8 ± 0.8, mean pulse height was 2.31 ± 0.52 ug/1; mean pulse width was 80.4 ± 2.3 min, and mean interpulse interval was 105.3 ± 2.8 min. Total IL-1α levels significantly correlated with those previously reported for IL-2 in the same samples, and IL-1α pulse parameters which are concentration independent were significantly similar to those of IL-2. Furthermore, cross-correlation analysis indicated that in 83% of our subjects (5/6) there was synchronicity of IL-1α and IL-2 levels. IL-1α pulse parameters were in the range reported for hormones which have well-characterized pulsatility, such as growth hormone, luteinizing hormone, follicle-stimulating hormone, cortisol, β-endorphin, and progesterone. Based on these data we speculate that a pulsatile cytokine cascade may exist in the systemic circulation. The presence of pulsatile IL-1α concentrations in the plasma of healthy women throughout the 24-hour period suggests that IL-1α may function as a classical hormone, being secreted into the blood stream and acting at distant sites, possibly as a component of the response to inflammation and to stress. The source of systemic IL-1α remains to be determined. Future studies of IL-1α blood levels should take into consideration these findings that circulating IL-1α levels exhibit pulsatility.