Mass mortalities of the ascidian Pyura stolonifera occurred along the Tsitsikamma coast in May 1991 and again in February 2012, following infection of large proportions of the population with a white microbial growth. P. stolonifera appeared to be the only species affected, with the outer tunic the main site of infection. No signs of pollution or algal blooms were observed, but large variations in climatic conditions were associated with both events. The 1991 mortalities occurred during a warm spell in autumn, when there was a rapid increase in the daily air temperatures. Similarly, the February 2012 event occurred after abnormally high air temperatures of January 2012 declined sharply due to a cold-water upwelling event in early February. These findings are compared with those of other marine disease and mortality studies.