The Muttahida Qaumi Movement, or MQM, said more than 40 party activists have disappeared since a police crackdown on government corruption began in November.
In response, the party ordered Karachi -- Pakistan's largest city with more than 9.3 million residents and the MQM's traditional power base -- closed Saturday in protest.
Public transportation ground to a halt and most shops and businesses remained closed for the day. The University of Karachi also closed for the day.
The MQM called Saturday a "day of mourning," Dawn News reported.