Introductory remarks the presentation of the E. Mead Johnson Award affords the recipient the honor of publicly acknowledging his debts to his teachers. I pay such grateful tribute to Dr. Grover Powers and Dr. Edward B. Shaw, my preceptors in academic pediatrics and to Dr. Joseph Smadel who introduced me to the pox viruses and urged me to take another look at the well-trodden field of smallpox. Helpful in his own way was the senior virologist who urged me instead to get involved in another, more fruitful field because "smallpox leaves no room for further work, having been well studied in the 1920's" and who, thereby, strengthened my resolve to re-examine current concepts in the field of smallpox and smallpox vaccination, a subject which has occupied us for the past 14 years. I also acknowledge my lasting debt to my associate, Dr. Henry Silver, who has been a critical colleague, supporter and friend over many years. The WELL KNOWN clinical observation that it is sometimes difficult to vaccinate the very young chi'd against smallpox led to our early assessment of passive immunity as a modifying factor1 and this, in turn, resulted in the development of hyper-immune vaccinal gamma-globulin and its use in the prevention of smallpox after known exposure.2 The principal subject of this report will be our therapeutic experience with hyperimmune vaccinal gamma-globulin in over 300 patients suffering from serious complications of smallpox vaccination. Finally, we hope to show how basic immunologic studies can be of great value in the management of some of the unfortunate patients whose experience with the vaccinia virus has been a tragic one.