Factors that contribute to the onset of milk production by the brood sac of the viviparous cockroachDiploptera punctatawere studied. Milk, which normally begins to be secreted on day 20 of adult age, was detected in brood sac tissue by rocket-immunoelectrophoresis. Humoral factors were shown to initiate milk synthesis in that: (1) brood sacs denervated on day 10 initiated milk synthesis normally, and (2) milk synthesis was initiated in brood sacs from 12-to 18–day donors after implantation into 50 day hosts (i.e., actively synthesizing milk). Implanted brood sacs from donors younger than day 10 did not produce milk suggesting that they were not competent to respond to the humoral factors within the host. Brood sacs from 15–day donors implanted into hosts with increasing levels of milk production contained milk in amounts that increased with that of the host. The humoral factors are not derived from the head because decapitation did not prevent the onset of milk synthesis. Milk production began, with a slight delay, in the presence of unfertilized eggs in the brood sac but did not continue to increase. This indicates that developing embryos are not needed to initiate milk production but are needed for its proper timing and subsequent potentiation. Thus, the onset of milk synthesis requires stimulation by humoral factors and development of the competence of the brood sac to respond to them.