Priapism is defined as a pathological condition where penile erection persists beyond, or is unrelated to sexual stimulation. In patients with ischaemic priapism, corporal blood aspirates are acidotic. One hypothesis for ischaemic priapism is reduced contractile function of cavernosal smooth muscle which may be secondary to this alteration in pH. This study aims to determine the effect of acidosis on nerve-mediated contraction in cavernosal smooth muscle and whether intracellular or extracellular pH changes mediate contractile alterations. Male Duncan-Hartley guinea pigs were humanely killed by cervical dislocation. Isometric contractions were recorded from strips of guinea pig corpus cavernosum in response to electrical field stimulation (EFS at 60 Hz, sensitive to 1 μM tetrodotoxin). Strips were superfused at 37°C with a HCO3^–/CO₂ buffered solution (pH 7.39). Acidosis in both the intra and extracellular compartments was generated by increasing the CO₂ content of the superfusate gas mixture from 5% to 10% (pH 6.99). [HCO3^–] was reduced in the superfusate in order to create an acidotic extracellular environment (pH 6.97). Intracellular acidosis was mimicked by increasing the CO₂ percentage and superfusate [HCO3^–] in proportion (pH 7.44). Total [Ca] was altered appropriately to maintain Ca²⁺ activity. Data are mean ± s.d. Statistical differences (p<0.05) between data sets were examined with Student's t tests. Acidosis induced in both compartments had no significant effect on the EFS response (after 60 mins. 103±12%, 120 mins. 100±11% of control, n=6). Furthermore, tension remained unchanged after 60 mins. of return to normal pH (100±11% of control). A reduction in extracellular pH alone significantly depressed tension (after 60 mins. 73±12%, 120 mins. 68±15% of control, n=6). After reperfusion with control superfusate for 60 minutes tension partially recovered to 82±11% of control. By contrast, alteration of intracellular pH significantly augmented tension after 60 min (110±4% of control, n=6). This increase was not sustained at 120 mins. (103±6% of control, n=6). Tension remained unchanged after 60 minutes of reperfusion (90±8% of control) Corporal blood aspirates from patients with ischaemic priapism show evidence of hypoxia, glucopenia and acidosis. This study would suggest that the detrimental effect of extracellular acidosis on nerve-mediated contraction of cavernosal smooth muscle appears to be ameliorated by the effect of a reduction in intracellular pH. The mechanisms by which intracellular acidosis exerts this protective effect and whether this is sustained in the presence of the other components of ischaemia needs to be assessed.