Recent studies indicate disruptions to the circadian system in brain injury and neurodegeneration. The results, however, are often not consistent and limited by measurement of only one circadian marker and by infrequent sampling rates. In this study, we examined diurnal rhythmicity in different stages of Huntington (HD) disease and in patients with acute moderate ischemic stroke (AIS) outside the retinohypothalamic pathway by evaluating serum concentrations of melatonin and cortisol at twelve timepoints. All study participants were subjected to the same study protocol of 12-hour light/dark cycle and controlled room conditions. Using cosinor analysis of data and comparing the results with the controls we found melatonin phase delay with lowered amplitude and mesor in stage III HD patients. These changes coexisted with phase advanced rhythm and elevated values of mesor and amplitude for cortisol. Early and mid-stages of HD showed only a phase advance in cortisol secretion. In AIS the circadian rhythm of serum melatonin was sustained without any phase shift and exhibited more flattened profile (lowered mesor and amplitude values), while advanced rhythm with higher mesor for cortisol was present. In conclusion, 1) abnormal pattern of melatonin release in the late stages of HD and in moderate AIS occurs in conjunction with phase-advanced rhythm of cortisol; 2) changes observed in late stages of HD are similar to those that occur with ageing; 3) brain regions other than the presumptive retinopineal neural pathway may play an important role in the pineal production of melatonin in humans; 4) lesion in extrahypothalamic region is related to the strong adrenal stimulation in response to AIS.