The circadian rhythm of stroke and myocardial infarction (MI) may be related to the circadian rhythm of melatonin, and erythrocyte deformability may be the key mechanism in this relationship. Therefore, this study has been performed to determine if there is a relationship between the pineal gland and melatonin and red cell deformability. Twenty-eight rats underwent pinealectomy, pinealectomy plus melatonin administration (200 mg/kg), or no treatment (n=7 in each group). Erythrocyte deformability was determined using the filtration technique. The results are reported in mean (+/-SD) seconds: control: 1.45+/-0.44; pinealectomy (A): 1.55+/-0.16; pinealectomy (B): 1.34+/-0.26 and pinealectomy and melatonin: 2.56+/-0.69. Pinealectomy by itself did not cause any statistically significant change in erythrocyte deformability but the addition of melatonin significantly decreased it. These results suggest a relationship between melatonin and erythrocyte deformability. Further investigations may uncover the causes of the circadian rhythm of stroke and MI, which may help improve chronobiological therapies.