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The optimum conditions for delay of implantation by hypophysectomy and neurodepressive agents are described. Hypophysectomy on day 1 without hormone replacement was followed by retarded development and subsequent degeneration of zygotes. Viability of blastocysts was maintained under these conditions by a single injection of a long-acting progestagen on day 1. Hypophysectomy at intervals beginning late on day 3 indicated that implantation is initiated by pituitary activity in the several hours around midnight of this day. In animals induced to ovulate and copulate by exogenous gonadotrophin injections, the corresponding time of pituitary activity was delayed by approximately 8 hr. This delay could not be explained solely on the basis of altered times of ovulation. It is evident that the events of early pregnancy do not follow the normal physiological pattern under these conditions, and caution should be exercised in utilizing such animals.

Of five neurodepressive agents examined, only trifluoperazine effectively delayed implantation. The effect of this substance injected at various times on day 3 of pregnancy suggests that implantation in the mouse is initiated by neurally regulated pituitary activity between 16.00 and 24.00 hr. on this day. Comparison with the mechanism of ovulation indicates that ovulation and implantation are regulated by separate hypothalamic-pituitary events, one peculiar to the oestrous cycle, the other to early pregnancy.