The sinus node of the dog was examined, using a large-specimen resin-embedding method for combined light and electron microscopy, after 30-240 min of total in vitro ischaemia and after 15-180 min of reduced blood flow in hearts with 2:1 AV block. Although progressive fine structural alteration was observed in the in vitro series, not all cells developed changes at the same rate. Complete loss of glycogen stores and swelling of organelles could be seen in many after only 30 min, whilst others retained their glycogen and showed minimal alteration even after 90 min. Despite relatively severe alteration throughout the node after 120 or more min, some groups of cells showed more extreme degrees of swelling and surface bleb formation than others. In the partially ischaemic in vivo series focal alteration, consisting chiefly of mitochondrial swelling and/or gross dilatation of sarcoplasmic reticulum vesicles, was detectable after 20 min and increased little in extent or degree during longer periods of reduced blood flow. This non-uniform response of sinus nodal cells to ischaemic injury parallels that of contractile atrial muscle cells.