Hi, I'm running Galaxy 16.01 behind Nginx 1.4.6 on Ubuntu 14.04 and I came across an issue where uploading files larger than ~3GB via the API into histories and libraries fails. Steps to reproduce (using BioBlend 0.7.0): from bioblend.galaxy.objects import GalaxyInstance gi = GalaxyInstance("galaxy-dev", "api_key") h = gi.histories.create() h.upload_dataset('/path/to/multigigabytefile') Observed results: ConnectionError: Unexpected response from galaxy: 504: <html> <head><title>504 Gateway Time-out</title></head> <body bgcolor="white"> <center><h1>504 Gateway Time-out</h1></center> <hr><center>nginx/1.4.6 (Ubuntu)</center> </body> </html> It looks like Nginx is accepting the full incoming data transfer over the network and saving it to disk successfully, and the error occurs during the subsequent forwarding of the request to Galaxy. There doesn't seem to be a particular threshold for file size (for example, 2GB and 2.7GB file can be uploaded successfully). Also, large file uploads do work when Galaxy is not running behind Nginx. Relevant log entries and config details are attached. I'd appreciate any help. Thanks, Ilya