The purpose of this study was to examine possible peripheral mechanisms for the reduction of propofol injection pain by the addition of ketamine. We hypothesised that pH changes associated with the addition of ketamine to propofol decrease propofol-induced pain on injection. We compared the efficacy of intravenous ketamine pretreatment under tourniquet with ketamine added to the propofol. In the pre-treatment group, patients received ketamine 10 mg in a total volume of 1.0 ml with 0.9% saline (n = 94; Group P) under tourniquet for 30 seconds before administration of propofol after release of the tourniquet. In the mixture group, propofol 9 ml was mixed with ketamine 10 mg in 0.9% NaCl 1.0 ml (n = 94, Group M). Pain was assessed with a four-point scale: 0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = severe pain at the time of propofol injection. The pH of propofol, ketamine and a range of propofol-ketamine mixtures were also measured. Forty-eight patients (51%) in Group P complained of pain on injection compared with 28 patients (30%) in Group M (P = 0.005). The pH of the 1% propofol-ketamine mixture was 5.84 while 1% propofol had a pH of 7.86. Our results support pH changes as a more important cause for the decrease in propofol injection pain with the addition of ketamine to propofol than a peripheral effect of ketamine.