Cross-tolerance to epidural morphine after prior systemic morphine therapy was studied in 26 cancer patients treated for relief of pain secondary to metastatic disease. A 'tolerance index' was calculated for each patient by multiplying the duration of previous morphine therapy with the daily dose just prior to the study and then compared with changes in the following variables measured after epidural morphine administration: with pain scores on a scale from 0 (no pain) to 10 (maximal pain), heart rate, blood pressure, respiratory rate and minute volume, arterial blood gas tensions of oxygen and carbon dioxide and arterial pH. There was no significant analgesic cross-tolerance to epidural morphine, but clear evidence for cross-tolerance regarding morphine's respiratory depressant action. The duration of the previous morphine therapy exerted a greater influence on the development of ventilatory cross-tolerance than the dose.

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