Circannual rhythmicity in plasma catecholamines is well known, but no chronobiologic data are available on endothelin-1 and angiotensin II. This study was designed to investigate in healthy human subjects whether endothelin-1 and angiotensin II exhibit seasonal variations. Furthermore, we assessed the relation of both variables to plasma catecholamines, to environmental temperature, and to relative humidity in northern Germany, a region of a temperate climate. Plasma concentrations of endothelin-1, angiotensin II, epinephrine, and norepinephrine were prospectively determined in venous blood from 10 healthy subjects at monthly intervals during 13 consecutive months. The single-cosinor method was applied to evaluate the seasonal rhythmicity of these parameters and to assess their temporal relation to both relative humidity and ambient temperature. Whereas relative humidity did not significantly change throughout the year, outdoor temperature was lowest in January and highest in August. Endothelin-1 levels displayed a significant variation, with a sinusoid pattern throughout the year: nadir values occurred in January, peak values in July. Angiotensin II demonstrated a significant correlation with endothelin-1 and paralleled its rhythmicity. In contrast, the two plasma catecholamines exhibited an opposite pattern. We noted a significant inverse correlation between endothelin-1 and norepinephrine. Outside temperature correlated positively with endothelin-1 and angiotensin II levels and correlated negatively with levels of both catecholamines. This is the first study to report a seasonal variation of endothelin-1 and angiotensin II in normal subjects. According to our data, environmental temperature is the climate variable most closely related to the rhythmicity of endothelin-1, angiotensin II, epinephrine, and norepinephrine.