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1. Prostaglandin E₁ or E₂ has two clearly distinguishable effects on the guinea-pig myometrium in vitro.

2. The first of these, the `direct' effect, is manifested by contraction accompanied by spiking, is readily modified by changes in the concentrations of Mg²⁺, Ca²⁺ and K⁺ in the suspension medium, and does not long outlast the presence of the prostaglandin in the organ-bath. In this respect it resembles the responses to other stimulants.

3. The second effect is manifested by `enhancement' of the responses to non-specific stimulation, whether this be by chemical or electrical means. Enhancement may be demonstrated for up to 20-80 min after the PGE₁ or PGE₂ has been washed out of the organ-bath, and during this time the myometrium shows no consistent changes in electrical activity or in resting mechanical tension that may be associated with the enhancement effect. Enhancement following PGEs is not readily affected by moderate changes in the Mg²⁺, Ca²⁺ or K⁺ concentrations of the suspension medium, and in all these respects it differs markedly from the effects of other stimulants.

4. K⁺-depolarized myometrial preparations show feeble direct responses to PGEs, like those to other stimulants. They also show post-PGE enhancement of the responses to other stimulants, but not of the responses to electric field stimulation.

5. The empirical method used for measuring the enhancement effect is examined critically.

6. The possible mechanisms of the direct and enhancement effects are discussed. It is postulated that they involve actions at two different sites, which may be on two different types of cell but are more likely to co-exist on the same cells. The direct effect is postulated to result from depolarization at the exposed cell membrane, whereas enhancement may result from facilitation of excitation—contraction coupling.