Cerebrolysin is an aqueous protein-free solution produced by biotechnological methods, using a standardised enzymatic breakdown of lipid-free pig brain proteins. The present study investigated the behavioural effects of this peptide derivative PD (100 mg/kg b.wt.), a related experimental peptide derivative PD-exp (1 mg/kg b.wt.) and a 0.9% saline control, on passive avoidance reaction (PAR) of 24-month-old male and female rats. Rats were pre-treated chronically for 7 days. Passive avoidance procedure started one day after the last subcutaneous injection with a single PAR-acquisition training session. Animals were trained in a step-through avoidance task using an unavoidable footshock of 1 mA (2 s). PAR-extinction testing showed that PAR latencies were treatment dependent (p < 0.001) due to the fact that PD and PD-exp treated animals displayed better performance. The same was true for all other behavioural elements observed. In this study we were able to demonstrate that s.c. administration of PD and PD-exp changes the capability of old female but not of old male rats to extinguish step-through behaviour. Because there were no differences in postshock latencies between control females and males we propose different sensitivity for the substances used.