Aims: To investigate whether non-preconditioned yeast cells survive under heat shock, when placed in growth medium originated from protected cells and to provide insights into the ionic contribution in the response. Methods and Results: The heat shock response was investigated by determining cell viability following exposure of yeast cells to 53degreesC for 30 min, either in the absence or presence of drugs. Preconditioning was performed by incubating the cultures at 37degreesC for 2 h. Under heat shock, non-preconditioned cell survival was significantly enhanced by the presence of the cell-free supernatant of resistant cultures. Addition of omeprazole or tetraethylammonium ions during the heat shock resulted in similar increases. Neither amiodarone nor mepivacaine showed any analogous effect. Omeprazole enhanced survival when added before the heat shock, while amiodarone exhibited a cytocidic action. Conclusions: Rapid balancing of ions may contribute to cell survival during heat shock, while survival under mild stress could probably be co-ordinated by additional events. Significance and Impact of the Study: Evidence is provided for the implication of the external environment and ionic homeostasis in the survival of yeast cells under unfavourable environmental conditions. This knowledge may be of importance in controlling both fermentation and therapeutic approaches.