This work was planned to investigate the correlation between humoral immune response, clinical and subclinical infection and the possibility of using ELISA test for diagnosis of caseous lymphadenitis (CLA) also, to evaluate the role of four types of vaccines in killing activity of macrophages. Twenty serum samples were collected from sheep showing clinical lesions suspected to be caseous lymphadenitis, also, twenty serum samples were collected from apparently normal incontact sheep and twenty control sera were collected from 6 month-old sheep living in free area. The serum samples of control group were used for calculation of the cut off values for ELISA antigens. Out of the twenty bacteriologically examined swabs collected from caseated lymph nodes, three isolates of C. pseudotuberculosis were recovered. Out of serologically examined 20 serum samples collected from sheep with characteristic CLA lesions, 18 serum samples were found positive by using Phospholipase D (PLD) antigen and 11samples were found positive when the somatic antigen was used as a coating antigen. On the other hand, incontact sheep sera showing positive results in 18 out of 20 sera when examined against PLD and 8 were positive when examined against somatic antigen. The killing activity of peritoneal macrophages collected from all groups of vaccinated to recipient mice received living C. pseudotuberculosis was estimated and the obtained results were as follows: Group of recipient mice inoculated with macrophages sensitized with combined vaccine (phospholipase D+ Bacterin) yielded 7 bacterial colonies compared with 23 colonies in control mice received living C. pseudotuberculosis only. Group of mice inoculated with macrophage sensitized with toxoid (PLD) yielded 3 bacterial colonies compared with 58 colonies in control mice. The third group which was sensitized with Bacterin yielded 46 colonies compared with 58 bacterial colonies in control mice. The fourth group which comprise living C. pseudotuberculosis sensitized macrophages recorded 11 bacterial colonies in recipient mice and 55 bacterial colonies in control mice.