OBJECTIVE Since erythropoietin (Epo) presents a diurnal rhythm in its circulating serum levels and it is reported increased in patients with chronic obstructive pulmonary disease (COPD), the circadian rhythm of Epo was investigated in a group of 40 normocytemic patients with chronic obstructive pulmonary disease compared with 40 clinically healthy subjects. METHODS Venous blood samples were drawn in each subject during the span of a whole day every four hours, starting from midnight, for the determination of serum Epo levels by RIA. Statistical analysis was carried out by chronograms and by means of the "cosinor" method. RESULTS The control group presents a significant (p < 0.001) circadian rhythm in serum Epo levels, with maximum in the afternoon, whereas no rhythm (p > 0.05) is detected in the patient group. This has significantly (p < 0.05) higher mean daily levels and lower diurnal variations of serum Epo than the control group; a significant (p < 0.05) difference exists between the two groups regarding the peaks of rhythms. CONCLUSIONS These data confirm the presence of circadian rhythm in serum Epo levels and suggest that the COPD, by daytime hypoxemia with associated severe nocturnal desaturation, is associated with increased serum Epo levels both by day and by night, so that the physiological circadian rhythm is lost in these patients.