Abstract An analysis of some of the factors that might prevent optimum response to the bacterial antigen (“vaccine”) therapy of low grade chronic (“focal”) infections reveals the following possibilities: The cultures may be taken from unsuitable foci. The recovery of organisms of suitable antigenicity may not always coincide with clinical expectations. The cultural procedure may be inadequate from the standpoint of the technique of isolation, the method of selecting the colonies, the incubation period, taxonomic considerations, and the methods used to differentiate the etiologic bacteria from contaminants. The culture selected may not possess suitable antigenic properties. The antigen may be injured during the cultivation process or in the later manipulation. The injured antigen may contain an excessive ratio of protein to specific antigen, causing it to be toxic and nonspecific. The dosage may be unsuitable. The injections may be given too often or the amounts may be too large. In other instances the doses may be too small for adequate stimulation of antibodies. The use of a fixed schedule is condemned. The condition of the patient may not be favorable for optimum antibody response because of endocrine or nutritional deficiencies, liver dysfunction, an excessive toxic load (e.g., an untreated focus), or other factors.