The objective of this study was to compare patients' hospital course, complications, and charges for oral and intravenous (i.v.) desensitization regimens for the treatment of syphilis in the penicillin-allergic gravida. We performed a retrospective search of medical records at two tertiary-level teaching hospitals and reviewed the hospital course of penicillin-allergic gravidas who underwent penicillin desensitization. Between August 1988 and December 1995, 16 procedures for penicillin desensitization were carried out: 11 oral procedures, and 6 i.v. procedures. There were no significant differences between the patients in the oral and i.v. desensitization groups with respect to demographic characteristics, duration of time in a monitored bed, or length of hospital stay. The oral regimen was less expensive than the i.v. regimen ($144.06 vs. $319.48). In our experience, oral and i.v. regimens provide effective desensitization for the treatment of syphilis in penicillin-allergic gravidas. However, the oral route offers ease of administration and substantial cost savings, making it the preferred method.